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Publication : Species-specific mechanisms control the activity of the Pit1/PIT1 phosphate transporter gene promoter in mouse and human.

First Author  Palmer G Year  2001
Journal  Gene Volume  279
Issue  1 Pages  49-62
PubMed ID  11722845 Mgi Jnum  J:73343
Mgi Id  MGI:2154904 Doi  10.1016/s0378-1119(01)00747-8
Citation  Palmer G, et al. (2001) Species-specific mechanisms control the activity of the Pit1/PIT1 phosphate transporter gene promoter in mouse and human. Gene 279(1):49-62
abstractText  The Pit1 phosphate transporter is involved in regulated phosphate handling in bone forming cells. In this study, we compared the structure of the murine and human Pit1/PIT1 promoters and characterized cis-acting elements controlling Pit1/PIT1 expression. The Pit1/PIT1 promoter sequence and its location relative to the first transcribed exon are conserved and similar transcription factor binding sites are found at identical positions in mouse and human. Luciferase reporter gene assays in transiently transfected mouse ATDC5 chondrocytes and human SaOS-2 osteoblasts indicated that the activity of the mouse Pit1 promoter depends on several cis-acting elements, including ATF/CREB, Sp1 and AP-1 sites, an E-box and a TATA box. In contrast, the activity of the human promoter essentially requires a TATA-like sequence and one single Sp1 site. This Sp1 site binds Sp1, Sp3, as well as unidentified proteins present in SaOS-2 nuclear extracts and co-transfection experiments in SL2 cells indicate that Sp1 and Sp3 activate transcription from the human PIT1 promoter. These data suggest that, despite similarities in promoter structure, changes in the relative importance of conserved transcription factor binding sites cause species-dependent differences in Pit1 promoter function, which allow Sp1-related proteins to play a particularly important role in human.
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